Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antigen presentation at the maternal-fetal interface has been characterized by a reported lack of classical MHC class I products and the presence of a tissue-restricted, non-classical class I product with limited polymorphism, HLA-G. The lack of HLA-A, -B, and -C products at this interface would allow escape from T-cell mediated attack, while the presence of HLA-G may enable evasion of NK cell-mediated destruction. We provide evidence that in addition to HLA-G, the classical class I product HLA-C is also present in trophoblast. Specifically, cDNA from the trophoblast-derived JEG 3 cell line encodes the HLA-C-locus product, HLA-Cw*0401. This protein, obtained by in vitro transcription/translation, has biochemical characteristics identical to MHC class I products immunoprecipitated directly from the same cells. These findings are in agreement with RNA analysis and immunohistochemistry on both cell lines and primary trophoblast tissues. We report here the preferential reactivity in JEG 3 cells of two widely used monoclonal anti-MHC class I heavy chain antibodies, HC10 and HCA2, with HLA-C and HLA-G, respectively. We have mapped the epitopes recognized by these reagents to distinct areas of the alpha1 domain of the MHC class I heavy chain. HCA2 recognizes the motif xLxTLRGx spanning amino acids 77 84 present in both HLA-A and HLA-G. In contrast, HC10 may recognize a discontinuous epitope, with essential elements of the recognized motif surrounding residue 60 in the alpha1 domain of the class I heavy chain, as shown by truncation analysis. These results adequately explain the immunochemical cross-reactivity of HLA-A and HLA-G.
Mol Immunol 1998 Feb
PMID:Why certain antibodies cross-react with HLA-A and HLA-G: epitope mapping of two common MHC class I reagents. 969 18

The crystal structure of the mouse major histocompatibility complex (MHC) class I molecule H-2Dd with an immunodominant peptide, designated P18-I10 (RGPGRAFVTI), from human immunodeficiency virus envelope glycoprotein 120 was determined at 3.2 A resolution. A novel orientation of the alpha3 domain of Dd relative to the alpha1/alpha2 domains results in significantly fewer contacts between alpha3 and beta2-microglobulin compared with other MHC class I proteins. Four out of ten peptide residues (P2 Gly, P3 Pro, P5 Arg and P10 Ile) are nearly completely buried in the Dd binding groove. This is consistent with previous findings that Dd exploits a four-residue binding motif comprising a glycine at P2, a proline at P3, a positively charged residue at P5, and a C-terminal hydrophobic residue at P9 or P10. The side-chain of P5 Arg is directed toward the floor of the predominantly hydrophobic binding groove where it forms two salt bridges and one hydrogen bond with Dd residue Asp77. The selection of glycine at P2 appears to be due to a narrowing of the B pocket, relative to that of other class I molecules, caused by Arg66 whose side-chain folds down into the binding cleft. Residue P3 Pro of P18-I10 occupies part of pocket D, which in Dd is partially split by a prominent hydrophobic ridge in the floor of the binding groove formed by Trp97 and Trp114. Residues P6 through P9 form a solvent-exposed bulge, with P7 Phe protruding the most from the binding groove and thereby probably constituting a major site of interaction with T cell receptors. A comparison of H-2Dd/P18-I10 with other MHC class I/peptide complexes of known structure provides insights into the possible basis for the specificity of the natural killer cell receptor Ly-49A for several related class I molecules.
J Mol Biol 1998
PMID:Three-dimensional structure of H-2Dd complexed with an immunodominant peptide from human immunodeficiency virus envelope glycoprotein 120. 976 82

1. Human medulloblastoma (ONS-76), a central nervous system (CNS)-derived undifferentiated cell line, was found to possess glial characteristics as defined by responses in the interferon (IFN) system; ONS-76 cells produced as much IFN-beta as human fibroblast and glioma cells by viral infection and poly(I):poly(C) induction. 2. Major histocompatibility complex (MHC) class I antigens were also induced under IFN-beta stimulation. ONS-76 cells expressed neurofilament protein, as shown by Northern blot analysis, and morphological differentiation was induced by dibutyryl cyclic AMP (dcAMP). 3. Expression of IFN-beta and MHC class I antigens was suppressed in ONS-76 cells during the dcAMP-induced differentiation. 4. These results showed that ONS-76 cells possessed a glial property in IFN system responses and a neuronal property in cytoskeleton protein, suggesting that the precursors of medulloblastoma may be characterized as bipotent neuronal and glial progenitors in CNS.
Cell Mol Neurobiol 1998 Oct
PMID:Interferon yield and MHC antigen expression of human medulloblastoma cells and its suppression during dibutyryl cyclic AMP-induced differentiation: do medulloblastoma cells derive from bipotent neuronal and glial progenitors? 977 50

The presentation of viral antigens on MHC class I molecules requires their intracellular fragmentation into peptides of appropriate length and anchor residue positions. Evidence has accumulated that the proteasome is the endoprotease in charge of the generation of MHC class I ligands in the cytoplasm. The generation of T cell epitopes derived from the leader peptides of endoplasmic reticulum (ER) targeted proteins, however. has been reported to be independent of the proteasome. Here we show that the H-2Db restricted antigen presentation of the immunodominant T cell epitope derived from the ER leader of the glycoprotein of lymphocytic choriomeningitis virus (LCMV) is completely abolished by administration of the proteasome inhibitor lactacystin. Thus our data support the role of the proteasome in class I restricted antigen processing and extend it to an ER leader derived epitope from a viral glycoprotein.
Mol Immunol 1998 Jul
PMID:The proteasome inhibitor lactacystin prevents the generation of an endoplasmic reticulum leader-derived T cell epitope. 982 57

Major Histocompatibility Complex (MHC, HLA in humans) class I antigens play an important role in cellular immunology by presenting antigens to T cells. Downregulation of MHC class I expression is thought to be a mechanism by which tumor cells escape from T cell-mediated lysis. In primary human melanomas and melanoma cell lines, HLA-B expression is frequently downmodulated, correlating with elevated expression of the c-myc oncogene. Transfection experiments have shown that c-myc induces HLA-B downregulation through a -68 to +13 base pairs (bp) core promoter fragment, containing CCAAT and TATA-like (TCTA) boxes. Since (i) c-myc has been reported to activate the human p53 promoter and (ii) p53 is capable of repressing a large array of basal promoters, we investigated whether c-myc-induced HLA-B abrogation is mediated by p53. In this article, it is shown that the HLA-B core promoter is indeed repressed by wild-type p53, making p53 a candidate for mediating c-myc-induced HLA-B downregulation. However, transfection of c-myc into p53-null cell lines still resulted in suppression of the basal HLA-B promoter, demonstrating that c-myc and p53 repress the minimal HLA-B promoter through independent mechanisms.
Mol Immunol 1998 Sep
PMID:Repression of the minimal HLA-B promoter by c-myc and p53 occurs through independent mechanisms. 983 51

The cDNAs for interferon-gamma (IFN-gamma) and allogeneic H-2Kd molecules were transfected into highly metastatic B16F10 melanoma cells (H-2b), and the synergistic effects of the antitumor immune responses by the doubly transfected cells (B16/Kd/IFN-gamma cells) were investigated in C57BL/6 mice (H-2b). The singly transfected B16F10 cells with either IFN-gamma or H-2Kd cDNA (B16/IFN-gamma or B16/Kd cells) were used as controls. The B16/Kd/IFN-gamma cells secreted biologically active IFN-gamma, and strongly expressed both syngeneic and allogeneic MHC class I antigens (H-2Kb and H-2Kd) on the same cell construct. Immunization with the doubly transfected B16/Kd/IFN-gamma cells induced higher anti B16F10 cellular cytotoxic responses than the single transfected B16/IFN-gamma or B16/Kd cells. Lyt-2.2 (CD8)+ T-cells were a major effector cell-type involved in the anti B16F10 responses and their cytotoxic activities were augmented in the immunized mice with the B16/Kd/IFN-gamma cells, as demonstrated by in vitro depletion experiments. The survival period of melanoma-bearing mice treated with the B16/Kd/IFN-gamma cells was significantly longer than that treated with the B16/IFN-gamma or B16/Kd cells. Furthermore, the treatment with the B16/Kd/IFN-gamma cells was capable of greatly inhibiting lung metastasis from small, established B16F10 footpad tumors. These results suggest that the augmented immunotherapeutic potentials can be achieved by the vaccination with IFN-gamma and allogeneic MHC class I genes transfected B16F10 melanoma cells.
Mol Cells 1998 Oct 31
PMID:Augmentation of therapeutic antitumor immunity by B16F10 melanoma cells transfected by interferon-gamma and allogeneic MHC class I cDNAs. 985 53

We have conducted an extensive phylogenetic analysis of polymorphic alleles from human and mouse major histocompatibility complex (MHC) class I and class II genes. The phylogenetic tree obtained for 212 complete human class I allele sequences (HLA-A, -B, and -C) has shown that all alleles from the same locus form a single cluster, which is highly supported by bootstrap values, except for one HLA-B allele (HLA-B*7301). Mouse MHC class I loci did not show locus-specific clusters of polymorphic alleles. This was considered to be because of either interlocus genetic exchange or the confusing designation of loci in different haplotypes at the present time. The locus specificity of polymorphic alleles was also observed in human and mouse MHC class II loci. It was therefore concluded that interlocus recombination or gene conversion is not very important for generating MHC diversity, with a possible exception of mouse class I loci. According to the phylogenetic trees of complete coding sequences, we classified human MHC class I (HLA-A, -B, and -C) and class II (DRB1) alleles into three to five major allelic lineages (groups), which were monophyletic with high bootstrap values. Most of these allelic groups remained unchanged even in phylogenetic trees based on individual exons, though this does not exclude the possibility of intralocus recombination involving short DNA segments. These results, together with the previous observation that MHC loci are subject to frequent duplication and deletion, as well as to balancing selection, indicate that MHC evolution in mammals is in agreement with the birth-and-death model of evolution, rather than with the model of concerted evolution.
Mol Biol Evol 1999 Feb
PMID:Locus specificity of polymorphic alleles and evolution by a birth-and-death process in mammalian MHC genes. 1002 82

We previously sequenced two regions around the centromeric end of HLA class I and the boundary between class I and class III. In this paper we analyze the two regions of about 385 kb and confirm, giving a new line of evidence, that the following two pairs of the genomic segments were duplicated in evolution: (i) a 43-kb genomic segment including the HLA-B gene showing the highest polymorphism among the classical HLA class I loci (class Ia) and a 40-kb segment including the HLA-C locus showing the lowest polymorphism and (ii) a 52-kb segment including the MIC (MHC class I chain related gene) B and a 35-kb segment including MICA. We also found that repetitive elements such as SINEs, LINEs, and LTRs occupy as much as 47% of nucleotides in this 385-kb region. This unusually high content of repetitive elements indicates that repeat-mediated rearrangements have frequently occurred in the evolutionary history of the HLA class Ia region. Analysis of LINE compositions within the two pairs of duplicated segments revealed that (i) LINEs in these regions had been dispersed prior to both the duplication of the HLA-B and -C loci and the duplication of the MICB and MICA loci, and (ii) the divergence of the HLA-B and -C loci occurred prior to the duplication of the MICA and MICB loci. To find novel genes responsible for HLA class I-associated or other diseases, we performed computer analysis applying GenScan and GRAIL to GenBank's dbEST. As a result, at least five as yet uncharacterized genes were newly mapped on the HLA class I centromeric region studied. These novel genes should be analyzed further to determine their relationships to diseases associated with this region.
J Mol Evol 1999 Mar
PMID:Genomic organization around the centromeric end of the HLA class I region: large-scale sequence analysis. 1009 21

The MHC class I complex, which binds and presents peptide antigen, is composed of a class I heavy chain and the beta2-microglobulin light chain. HIV-1, which induces a profound immunodeficiency in infected individuals, encodes proteins that cause decreased expression of class I heavy chain. We now report that the HIV Tat protein, which is a potent transactivator of viral transcription, is also a potent repressor of the beta2-microglobulin gene. Repression is mediated through the basal promoter of the beta2-microglobulin gene, which is shown to be predominantly regulated by an initiator element. Tat repression is further augmented by the short viral transcript, TAR, which interacts with Tat. Tat-mediated repression of beta2-microglobulin expression, together with its known repression of class I gene transcription, provides an effective mechanism by which HIV could prevent cell surface expression of the MHC class I complex and avoid immune surveillance.
Mol Immunol 1998 Dec
PMID:HIV Tat represses transcription of the beta 2-microglobulin promoter. 1019 91

Twelve cosmids containing sequences resembling genes encoding members of the 70-kDa heat-shock protein family, HSP70. have been isolated from Fugu rubripes. They can be broadly divided into three groups of overlapping cosmids. Restriction analysis and sequencing of one set of five cosmids have revealed five intronless Fugu HSP70 genes spanning 42 kb, arranged in a combined head-to-head, tail-to-tail and head-to-tail orientation. The levels of DNA and amino acid identity are very high with respect to one another, and are most similar to HSP70 sequences linked to the major histocompatibility complex (MHC) region in other species. Putative heat-shock consensus elements are identified. Non-HSP70 sequences with homology to known genes have been found physically linked to this Fugu HSP70 cluster: the Drosophila melanogaster SOL gene, the Drosophila melanogaster nemo gene, the Caenorhabditis elegans T17E9.1 gene and the sequence encoding the serine protease domain. The linkage relationships described here so far bear no resemblance to those of HSP70 in other organisms. Convergence of mammalian HSP70 and MHC class I and II loci probably occurred after fish had diverged.
Cell Mol Life Sci 1999 Apr
PMID:Short-range linkage relationships, genomic organisation and sequence comparisons of a cluster of five HSP70 genes in Fugu rubripes. 1035 35


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